[Source: Clinical Infectious Diseases, full page: (LINK). Abstract, edited.]
Clinical, virological, and histopathological manifestations of fatal human infections by avian influenza A(H7N9) virus
Liang Yu 1,2,*, Zhaoming Wang 3,*, Yu Chen 1,2,*, Wei Ding 3, Hongyu Jia 1,2, Jasper Fuk-Woo Chan 4, Kelvin Kai-Wang To 4, Honglin Chen 2,4, Yida Yang 1,2, Weifeng Liang 1,2, Shufa Zheng 1, Hangping Yao 1,2, Shigui Yang 1,2, Hongcui Cao 1,2, Xiahong Dai 1, Hong Zhao 1, Ju Li 5, Qiongling Bao 1,2, Ping Chen 1,2, Xiaoli Hou 6, Lanjuan Li 1,2, and Kwok-Yung Yuen 2,4
Author Affiliations: <SUP>1</SUP>State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China <SUP>2</SUP>Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, 310003, China <SUP>3</SUP>Department of Pathology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China <SUP>4</SUP>State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, China <SUP>5</SUP>Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China <SUP>6</SUP>Center of Analysis and Testing, Zhejiang Chinese Medical University, Hangzhou. 310003, China
Correspondence: Lanjuan Li. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, 79 Qingchun Road, Hangzhou, 310003, China. Phone: 86-571-87236458. Fax: 86-571-87236459. E-mail: ljli@zju.edu.cn, Kwok-Yung Yuen. Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Pokfulam, Hong Kong Special Administrative Region, China. Phone: 852-22554892. Fax: 852-28551241. Email: kyyuen@hkucc.hku.hk
* These authors contributed equally to this work.
Abstract
Background.
Systematic analysis of histopathological and serial virological changes of fatal influenza A(H7N9) cases is lacking.
Methods.
Patients with A(H7N9) infection admitted to our intensive care unit between April 10-23, 2013, were included. Viral loads in the respiratory tract, as inferred from the Ct value of RT-PCR, and the serum hemagglutination inhibition antibody titer, were analyzed. Postmortem biopsies of the lung, liver, kidney, spleen, bone marrow and heart were examined.
Results.
Twelve patients (six fatal cases, six survivors) were included. Median viral load was higher in sputa than the nasopharyngeal swabs for fatal cases (median Ct, 23 vs 30.5; P=0.08). RT-PCR for A(H7N9) was positive in stool samples (67%, 4/6) of fatal cases and (33%, 2/6) of survivors, but was negative in the cerebrospinal fluid, urine or blood of all patients. Nosocomial bacterial infections were more common in fatal cases than survivors (83% vs 50%). HI titer increased by ≥4-fold in those with convalescent sera. Postmortem biopsy for three patients showed acute diffuse alveolar damage. Patient 1, who died eight days after symptom onset, had intra-alveolar hemorrhage. Patient 2 and 3, who died 11 days after symptom onset, had pulmonary fibroproliferative changes. Reactive hemophagocytosis in the bone marrow and lymphoid atrophy in splenic tissues were compatible with laboratory findings of leukopenia, lymphopenia and thrombocytopenia. Hypoxic and fatty changes of kidney and liver tissues are compatible with impaired renal or liver function.
Conclusion.
Fatal A(H7N9) infection was characterized by viral and secondary bacterial pneumonia with 67% having positive RT-PCR in stool.
Received June 9, 2013. Accepted August 4, 2013.
? The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
For Permissions, please e-mail: journals.permissions@oup.com.
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Clinical, virological, and histopathological manifestations of fatal human infections by avian influenza A(H7N9) virus
Liang Yu 1,2,*, Zhaoming Wang 3,*, Yu Chen 1,2,*, Wei Ding 3, Hongyu Jia 1,2, Jasper Fuk-Woo Chan 4, Kelvin Kai-Wang To 4, Honglin Chen 2,4, Yida Yang 1,2, Weifeng Liang 1,2, Shufa Zheng 1, Hangping Yao 1,2, Shigui Yang 1,2, Hongcui Cao 1,2, Xiahong Dai 1, Hong Zhao 1, Ju Li 5, Qiongling Bao 1,2, Ping Chen 1,2, Xiaoli Hou 6, Lanjuan Li 1,2, and Kwok-Yung Yuen 2,4
Author Affiliations: <SUP>1</SUP>State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China <SUP>2</SUP>Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, 310003, China <SUP>3</SUP>Department of Pathology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China <SUP>4</SUP>State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, China <SUP>5</SUP>Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China <SUP>6</SUP>Center of Analysis and Testing, Zhejiang Chinese Medical University, Hangzhou. 310003, China
Correspondence: Lanjuan Li. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, 79 Qingchun Road, Hangzhou, 310003, China. Phone: 86-571-87236458. Fax: 86-571-87236459. E-mail: ljli@zju.edu.cn, Kwok-Yung Yuen. Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Pokfulam, Hong Kong Special Administrative Region, China. Phone: 852-22554892. Fax: 852-28551241. Email: kyyuen@hkucc.hku.hk
* These authors contributed equally to this work.
Abstract
Background.
Systematic analysis of histopathological and serial virological changes of fatal influenza A(H7N9) cases is lacking.
Methods.
Patients with A(H7N9) infection admitted to our intensive care unit between April 10-23, 2013, were included. Viral loads in the respiratory tract, as inferred from the Ct value of RT-PCR, and the serum hemagglutination inhibition antibody titer, were analyzed. Postmortem biopsies of the lung, liver, kidney, spleen, bone marrow and heart were examined.
Results.
Twelve patients (six fatal cases, six survivors) were included. Median viral load was higher in sputa than the nasopharyngeal swabs for fatal cases (median Ct, 23 vs 30.5; P=0.08). RT-PCR for A(H7N9) was positive in stool samples (67%, 4/6) of fatal cases and (33%, 2/6) of survivors, but was negative in the cerebrospinal fluid, urine or blood of all patients. Nosocomial bacterial infections were more common in fatal cases than survivors (83% vs 50%). HI titer increased by ≥4-fold in those with convalescent sera. Postmortem biopsy for three patients showed acute diffuse alveolar damage. Patient 1, who died eight days after symptom onset, had intra-alveolar hemorrhage. Patient 2 and 3, who died 11 days after symptom onset, had pulmonary fibroproliferative changes. Reactive hemophagocytosis in the bone marrow and lymphoid atrophy in splenic tissues were compatible with laboratory findings of leukopenia, lymphopenia and thrombocytopenia. Hypoxic and fatty changes of kidney and liver tissues are compatible with impaired renal or liver function.
Conclusion.
Fatal A(H7N9) infection was characterized by viral and secondary bacterial pneumonia with 67% having positive RT-PCR in stool.
Received June 9, 2013. Accepted August 4, 2013.
? The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
For Permissions, please e-mail: journals.permissions@oup.com.
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